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Friday, June 2, 2017

The healthy Kurgan pastoralist

Just in at bioRxiv, a new preprint on the genomic health of ancient hominins, at this LINK. Obviously, if it's true that the Yamnaya and other closely related Kurgan culture pastoralists of the ancient Eurasian steppe had unusually healthy genomes, then it becomes easier to understand why they made such a massive impact on the ancestry of present-day Europeans and Central and South Asians, because populations that enjoy good health are likely to grow faster than those that don't. From the preprint, emphasis is mine:

Abstract: The genomes of ancient humans, Neandertals, and Denisovans contain many alleles that influence disease risks. Using genotypes at 3180 disease-associated loci, we estimated the disease burden of 147 ancient genomes. After correcting for missing data, genetic risk scores were generated for nine disease categories and the set of all combined diseases. These genetic risk scores were used to examine the effects of different types of subsistence, geography, and sample age on the number of risk alleles in each ancient genome. On a broad scale, hereditary disease risks are similar for ancient hominins and modern-day humans, and the GRS percentiles of ancient individuals span the full range of what is observed in present day individuals. In addition, there is evidence that ancient pastoralists may have had healthier genomes than hunter-gatherers and agriculturalists. We also observed a temporal trend whereby genomes from the recent past are more likely to be healthier than genomes from the deep past. This calls into question the idea that modern lifestyles have caused genetic load to increase over time. Focusing on individual genomes, we find that the overall genomic health of the Altai Neandertal is worse than 97% of present day humans and that Otzi the Tyrolean Iceman had a genetic predisposition to gastrointestinal and cardiovascular diseases. As demonstrated by this work, ancient genomes afford us new opportunities to diagnose past human health, which has previously been limited by the quality and completeness of remains.
...
Both the allergy/autoimmune and gastrointestinal/liver disease categories (which share many of the same disease-associated loci) show significantly lower genetic risk in pastoralists than agriculturalists and hunter gatherers. Pastoralists also have significantly reduced risk for cancer compared to agriculturalists. Agriculturalists have a higher genetic risk for dental/periodontal diseases than hunter-gatherers and pastoralists. In general, pastoralists possess extremely healthy genomes, especially for cancers and immune-related, periodontal, and gastrointestinal diseases.
...
It is unclear why pastoralists would have the lowest risk in these specific disease categories. We caution that this pattern may be the result of technical issues, as pastoralists have the smallest sample size (only 19 individuals) and geographic range (between 40-90°E longitude and 45-55°N latitude, Figure 1B). Because populations that have different subsistence types also differ in other ways, the lower GRS of pastoral populations may be due to other factors, including demographic history.

I'm not sure their use of the genome to predict the health of Altai Neanderthals is valid:

"Here, we estimated that the Altai Neandertal genome has an elevated risk of neurological diseases (80th percentile compared to modern humans). This is consistent with previous findings from electronic health records and patient genomes that linked Neandertal haplotypes with increased risk for depression along with tobacco addiction, urinary tract disorders, and skin lesions (Simonti, et al. 2016)."

I think I remember that at least some have theorized these genes only are malicious in AMH, not necessarily in Neanderthals. So to speak because they are "running out of context".

Yeah, interesting to try, I'm not really sure I believe the results. Essentially, yes, led because the distribution of disease risk in modern populations doesn't follow distribution of steppe vs neolithic ancestry.

(If anything risk of CVD may to have a weakly opposite pattern in modern people - https://futurechallenges.org/wp-content/uploads/2013/07/mashapic.jpg / https://jakubmarian.com/wp-content/uploads/2016/11/mortality-cardiovascular-disease-europe.jpg).

Cancer is a surprise, with greater risks in tall people, and the pastoralist ancients were supposed to be taller.

Finally, if these are mostly common variants with fairly high frequencies, I am also not sure if they would have a wholly negative effect on fitness overall. Dental disease alleles may be associated to smaller teeth (less enamel, more decay, etc) and cancers to increased circulating sex and growth hormone (the two big hitters which account for the majority of cancer incidence, breast and prostate, both are).

Yes I'm somewhat cautious of some of the sugesstuons. Breast cancer alone has numerous loci and environmental contributors, eg. Outside obvious common Genomic mutations (BrCA, p53), the. main factor is increasing Age and menstrual history. Height is not a factor in carcinigenesis; but obesity is (common knowledge). They are a function of increasingly modern & sedentized lifestyle. Still, very interesting

Total body mass (goes up with both height and BMI) may be better than height, and taller people may not have a increased cancer risk against shorter people with the same TBM, but I believe height->cancer risk is pretty well replicated.

Matt:That CVD mortality map is basically screaming "non-genetic effect" with very sharp changes at country borders even where there is hardly any sharp genetic border. We do know these diseases very much effected by lifestyle, food and stress, ect...

I wonder if some of the studies showing correlation between height and Ca. corrected for ethnicity, BMI, and time (eg contemporary versus (say) 1960s individuals in retrospective analyses). I guess it might be linked to diet, as calorie depletion is said to be carcino-protective (by minimizing generation of free radical released during metabolism). Whatever the case, in clinical epidemiology talks it is BMI which is the most important 'physical trait' by far.

@Slumbery, true point; though we don't have fine grained enough genetic data to really totally 100% confirm that, I actually can't disagree with that on the basis of https://jakubmarian.com/wp-content/uploads/2016/11/mortality-cardiovascular-disease-europe.jpg which is actually fine scaled enough to relate to the question.

There is a rather large problem with this paper, they assume that the same disease related allelles have the same effects on ancient and modern populations. Have they not heard of lifestyle related disease?

Re: http://popgen.gatech.edu/ancient-health/, if they fix the interface up properly and put the whole table up, might be able to look at a finer grained distinctions that isn't in the paper.

I had a quick go at trying to match MN samples to Yamnaya samples, using the sampleIDs from Mathieson's supplement: http://imgur.com/a/EE2Ll

I quickly got a bit frustrated with it though, as they haven't put the samples in any kind of alphabetical order, and they have to be downloaded one at a time, so only gathered about 6 MN vs 7 Yamnaya.

Probably really you'd want at least 19 samples of MN to compare to their n=19 pastoralists (though you might have fewer pastoralists if you wanted to look at only Steppe_EMBA, as I think they have MLBA and Scythians here as well). Check out if differences in time and subsistence interact.

I do not understand what they try to say ? Do they mean that Pastoralist were exposed to this diseases more frequently earlier and managed to build a stronger immune system as a result ? The Steppe certainly had a less nutrition rich environment than most other places in Europe ?

It will be interesting to see the Comparison between Steppe Hunter Gatherers and their later descendants that adopted pastoralism in the same area.

Then we can see if people with unwanted genes were rooted out earlier during the Hunter Gatherer phase or early pastoral phase, or if they always had this genetic traits ? Or if the CHG admixture in Yamnaya created this genetic scenario....

It seems that the genes here form an interaction complex around immune function and inflammation, which would make sense as pastoralists would have larger population size than HGs and thus be better at purging genetic load, while also having smaller parasitic burden and thus require smaller evolutionary tradeoffs than agriculturalists.

There is an obvious problem with this paper. The ancient DNA is not coming from a random sample of the population. We know that Kurgans contain the elite of pastoral societies. There is every reason to expect that societal elites worthy of special burials would be healthier than the average population. Comparing to modern populations is therefore invalid. I'm not sure about comparison to farmer and hunter-gatherer ancient populations, as it depends on what social stratum their DNA is representing.

There are some genes that are associated with disease in Asian but with good health in Europeans and vice versa. Part of the environment that selects whether a gene is fit or unfit is the other genes on the genomes, so it is no surprise that other subspecies in the process of becoming another species ill have genes that are associated with bad health in your own sub species.

If pastoralists are indeed better looking there are plenty of other hypothesis to be thought of. The dependable nutrition provided by milk allows good looking genes to express themselves if good looking genes are hidden by malnutrition or small pox scars (prevented by cow pox) then they can not be selected for in mate selection a gene for handsomeness can only be an advantage if you avoid such mutilation.

Pastoralists are more mobile, the men have more honor killings than horticulturalist and raid more settled neighbors for women. So pastoral men have the pick of many women selecting the lookers. As their dairy herds can feed large families of healthy growing children more easily women are attracted to them, and the large family size lets them go through the war cycle more frequently, giving men the pick of the women.

Lukasz M said... Davidsky look at thathttps://indo-european.info/indo-european-demic-diffusion-model-2.pdfDavidski said... Why does one of the maps show a movement of R1b from Siberia to Europe via West Asia, when there's so much Mesolithic R1b in Eastern Europe?

Of course. We'll see next if the R1b subclades came from Eastern Europe as you think or if there were only some subclades of R-L23 (above all) but not the origin of the upstream and downstream subclades as I think. But we'll see that from the data, above all the aDNA. Why this paper (a thesis actually) says that R1b came from Iran? But because it quotes the papers of Underhill et al., I denounced as biased from the prejuduce that "Ex Oriente lux", which found many R1a-M420 in Iran, but it kept silent on the sample found in Italy, and also on the fact that Cruciani found "3 Italians, 1 West Asian, 1 East Asian" (p. 20) and which weren't "Basal R1b1-L278* lineage", but R-L389*, and Italy has the highest variance all over the world. They use the manipulation of the reality, as a paranoid who attacks me always uses. It wouldn't have been a refugium of R1b1 in Italy because the refugia were during the LGM, and in Italy has been found only 14000 years ago, but I never said that it was there before (we don't know), only that I believe that it was during the Younger Dryas and expanded after that. I'd be against YFull because I say that I exteem its dates underestimated for an 1.17 or 1.26 factor, but just because YFull put the separation from A00 and A0-T at 235900 years ago, whereas others as Poznik (also the last paper of Tyler-Smith) put it at 275000 years ago and Shi Huang at more than 300000. Of course I am not against YFull for that, because I always defended it from the attacks that it had in the past, and is having now, and you all know from whom. This paranoid uses manipulated tree, keeping off all what is against his agenda, and a moron says: "Well done Ted Kandell, in the Y-Tree here we see two surviving sons of L754 and so far no surviving down line of V88 on the tree. That's what I'm seeing", but only because he kept them off. Risum teneatis?

Great book quoted in the paper https://indo-european.info/indo-european-demic-diffusion-model-2.pdf

Gianfranco Forni Evidence for Basque as an Indo-European Language

Of course this strenghtens what I thought that Etruscan was "periindoeuropean" (Devoto) and that the Old Sardinian was linked to Basque, and all in a great area around the "Italian Refugium" from where the hg. R1b1 and the Indo-European languages came out. So the high percentage of R1b amongst the Basques isn't anymore strange.Great book!

What I do not understand is the story about the apparent barrier between East and West that was created by the Volga or Ural rivers during the Glacial meltdown.

Did people never learn to cross rivers before ? Wasn't there Winters that froze over rivers and marshes enabling people to cross the Ice ?

I think some people underestimate human capabilities. The people in the North surely were more adapted to a Cold Climate and a Warming Climate may even have encouraged them to also travel at Winter Times.

"What I do not understand is the story about the apparent barrier between East and West that was created by the Volga or Ural rivers during the Glacial meltdown."

The post about mammoths from a while back showed different clades of mammoth east and west of a line near the Urals.

So it might not have been a barrier to humans but a barrier to the animals they hunted - one population following the herds that kept to the west of the line and a second population following the herds that kept to the east of the line.

"here is evidence that ancient pastoralists may have had healthier genomes than hunter-gatherers and agriculturalists."

Really? Last time I checked Pastoralism was a agricultural technique. They probably mean cereal farmers.

Pastoralism is the branch of agriculture concerned with the raising of livestock. It is animal husbandry: the care, tending and use of animals such as camels, goats, cattle, yaks, llamas, and sheep. "Pastoralism" generally has a mobile aspect; moving the herds in search of fresh pasture and water (in contrast to pastoral farming, in which non-nomadic farmers grow crops and improve pastures for their livestock).

Confirming Tacitus' and Ptolemys demographic descritions - where the river Vistula represented a major divide between the occidental and the oriental

In Tacitus this divide is explained in etnographic terms as "germanic people" vs. "sarmatic". In the norse vocabulary the same area was called "Venland" and "Wendland" - from Vistula to the Finnish bay.

In Tacitus context "Sarmatia" would cover the same area, and then eastwards to Ashov as well as Asdrakan. The first travel and traade along Eurasias largest river-routes - since late Mesolihic.

Thus we may induce that A east-west divide between "etnicities" as well as "language-groups" have followed the Vistula since the Ahrensburg-Swidrien divide.

@Richard HoltmanCertainly compared to to the wiry and stunted neolithic farmers and swarthy and malnourished HG cavemen these indo-european warriors fire up the imagination of any ethnicist of the Steppe-stock. But joking aside, I'm surprised that even the HGs were more sickly than the steppe nomads. I guess the dwindling ecological niches and inbreeding among the survivors did their trick.

Here's the big caveat to the "Healthy herders" conclusion. As has been previously mentioned, the lifestyles of all three of these ancient populations are vastly different from those of the modern sedentary populations in developed countries that these genetic health studies are based on. Many genes that are clearly deleterious today are also just as clearly very good for the health of ancient people. Light skin alleles are a massive cancer risk factor for European descended Australians who live near the equator. Studies of chronic disease and cancer rates in non industrialized communities often reveal starkly different patterns from those found in places like the USA. So how can we be sure that the disease risks of these genes are invariant with respect to different environments and life histories?

To me it looks like ancient pastoralists were under selection for genes that protect them from zoonotic disease and allow their digestive systems to process heavy loads of meat and dairy products. But paradoxically, greater genetic health could mean worse actual realized health outcomes, because groups experiencing environmental stress to their health undergo the relevant selection, and groups without these pressures allow the mutations to accumulate without being cleared out. That's why HGs are the least genetically healthy. For one thing, much smaller populations and pop density means much less infectious disease.

It's a fascinating study and it tells us about evolutionary processes in ancient populations. But I don't think we can know what the real health outcomes of these people were without looking at non genomic evidence.

That's an obvious asset to any arctic community - in use already during the paleolithic/mesolithic transition.

The first mesolithic settlers of Europe and Northern Asia made keels and skis.

From the first they made boats and (seaworthy) ships. From the latter they made sledges. Add domestcated dogs and you may have a highway along evry river of size - all year along.

We know for a fact that such river-routes were established between all major areas of mesolithic Eurasia. We even know that the evolution of these inland river-routes started with the Ahrensburg-Swidrien divide.

No doubt many people here are well intentioned--yet so much stuff here is absolutely facepalm-worthy. Adaptation to high parasitic load does not make you more adapted to the environment in a general sense, it makes you less adapted. If you have a physical and ecological environment A and another environment that is identical to A but full of parasites and transmissible diseases A', strong adaptation to A' will cause the population to be less adapted to A, not more. In fact if the selection is sufficiently strong, many otherwise deleterious alleles may spread if they confer some resistance to disease.

But paradoxically, greater genetic health could mean worse actual realized health outcomes, because groups experiencing environmental stress to their health undergo the relevant selection, and groups without these pressures allow the mutations to accumulate without being cleared out. That's why HGs are the least genetically healthy.

WTF?

HGs are extremely genetically unhealthy because their effective population size is absolutely tiny, not because of any other reason. For selection to purge alleles effectively, the population size as a rule of thumb has to be at least the reciprocal of the selection coefficient, and given that most alleles have low selection coeefficients, mildly deleterious alleles will tend to accumulate in HGs.

As I see it the Ice Melted over several thousand years. As the Ice receded plants that were adapted to the near Glacial environment also spread North and so did the animals that adapted to grazing on these plants. We see this with desertification also. As the environment change animals migrate to the area which is most similar to what they were used to. That is how Mammoths ended up on Islands near the Arctic...

Thanks for correcting that. So, what are your thoughts about the conclusions of this paper? If demographic effects are enough to explain the GRS distribution in Euro HG (Mota is included as well), what about the difference between the farmers and the pastoralists? What does this look like to you?

This analysis has way too many caveats. We have no data on the actual health of ancient peoples before the Bronze Age migrations. To suggest that Neanderthals were unhealthy because of inbreeding can not be proven.

Ashkenazi Jews have a quite small effective population size, but are doing quite well, and were also doing fine before modern medicine.

Quite the nonsequitur. Tiny inbred populations are not going to be genetically healthy, neither are populations under no selection pressure. So there is no conflict with the idea of genetic degeneration in modern times through lack of selection.